Alzheimer's disease (AD) is the most common progressive and currently irreversible form of dementia with symptoms like memory loss, personality changes, impaired judgment, disorientation and loss of language skills. Despite great efforts to understand the causes, there remains the challenge to develop novel agents for AD therapy. The aggregation of β-amyloid (Aβ) peptide, which is the major component of the toxic amyloid plaques, exerts a decisive role in the neuropathology of AD. The Aβ peptides, which differ in length from 38 to 42 amino acids, are generated from the amyloid precursor protein (APP,) by processing of two aspartic proteases: β- (BACE-1) and γ-secretase. As the γ-secretase mediates the critical step in the liberation of Aβ from the membrane it is an interesting target for the treatment of Alzheimer’s disease. Several γ-secretase inhibitors have been identified until now which reduce Aβ secretion sufficiently to alleviate the cause of AD. An unmeant adverse effect is abolishing of the processing of other proteins, which have important roles in neuronal structure and function. A promising class of substances, the gamma-secretase modulators (GSMs), were firstly identified as non-steroidal anti-inflammatory drugs which do not completely inhibit gamma-secretase. These modulators shift the cleavage site of the gamma-secretase from the toxic Abeta42 to the Abeta38 while processing of the other substrates remains unchanged. The N-alkylated carbazolic acids have been presented as potent modulators of γ-secretase. Two essential functional groups of these GSMs have been identified to be crucial for the modulating character: the lipophilic substituent and the carboxylic acid in the side chain. In the presented work these two functionalities were investigated concerning their properties and functions. The lipophilic substituent causes amphiphilic properties of the modulator, which may interact with membranes, and the carboxylic acid seems to interact with the binding site. Based of these two SARs a mode of action has been hypothesized of these investigated GSMs by an interaction with the substrate at lysine624. The membrane anchor seems to be essential for modulators orientation and thereby interrupting the interaction of two APP monomers to a dimer resulting in an increased Abeta38 level.